We are studying the molecular biology of tumor metastasis and invasion. We are using a variety of techniques to identify specific genetic elements whose expression is altered in metastatic cells. Pulse-labeling studies of paired benign and metastatic cells reveal differences in the synthesis of specific proteins. RNA from cultural cell lines and tissues with varying metastatic potential is being analyzed by cell-free translation in a rabbit reticulocyte lysate and by hybridization analysis. In vitro translation studies indicate that the levels of several specific mRNAs are either markedly increased or decreased in metastatic murine melanoma cells and in metastatic human breast carcinoma cells. Rot curve analysis of human breast carcinoma cDNA confirms that specific gene sequences are present in abnormal amounts in more malignant cells. We are in the process of constructing and screening recombinant DNA libraries of metastatic cDNAs to isolated and study specific genes involved in the etiology and maintenance of the neoplastic state.